Frog motor nerve terminals, contrary to common perception, are highly plastic in morphology and function. We have worked out many of the factors that regulate their properties. Further research is proposed in four areas: The first project is concerned with the fact that normal-appearing terminals or parts of terminals are sometimes found to release very little transmitter. As terminals grow and new junctions are added, apparently in response to signals from the muscle, a significant fraction (the distal 20-40%) of long terminal branches, and sometimes whole terminals, release only 5-10% as much as other terminal regions. It seems likely that these seemingly ineffective terminal regions may be functional under conditions we have not examined. We will test several hypotheses for possible functions of "silent" terminal components, and attempt to discover why they release so little transmitter under the conditions tested. A second project is aimed at understanding what causes the large increase in release efficacy of intact terminals in partially denervated muscle. This enhancement of release appears to precede sprouting. We will characterize it, attempt to determine what triggers it, and study possible mechanisms. We will also study the non-quantal "leak" of ACh from motor nerve terminals, using ultrasensitive ACh sensing probes made by patch clamping a small piece of muscle cell membrane containing ACh channels. With these probes, sensitive enough to detect single channel openings, we will study the dependence on quantal release levels, nerve activity, and external ionic environment. Finally, we will study the development of the highly organized innervation pattern of the Xenopus pectoralis muscle, in which single axons selectively innervate one of three types of twitch fibers, are topographically localized to a tightly restricted region of the muscle, and tend to selectively innervate both endplates on fibers. It is probable that this organization is functionally adaptive, and may be refined by use in a way comparable to that of CNS connections.